To date, no study has examined the onset of brain changes using functional neuroimaging in the acute aftermath of a traumatic event to identify the early antecedents of PTSD. Up to one third of people exposed to a motor vehicle accident (MVA) develop acute stress disorder, and approximately a third of these, progress to posttraumatic stress disorder (PTSD). The objective of this application is to discover the brain areas involved in pathological responses to traumatic stress. The two specific aimsare to identify brain regions functionally associated with: 1)acute stress disorder and specific acute stress symptomatology, and 2)the subsequent development of PTSD. Design/Methods: Seventy MVA victims (50 with and 20 without acute stress disorder) will be recruited consecutively from a community hospital emergency room and evaluated with clinician assessments, standardized psychometrics, and acoustic startle within 2 weeks after the MVA. All subjects will undergo pairs of two neutral script and symptom provocation PET scans using [S15O]-H2O at 2 weeks post-MVA. At three months post-MVA subjects will have clinician assessments (CAPS) for PTSD. This project is highly innovative since it is the first study to examine early functional brain abnormalities in the acute aftermath of a traumatic event. We expectto find that certain symptoms clusters are associated with amygdala and/or hippocampal differences; and that subjects who do not have remission of their symptoms by 3 months will have had prefrontal abnormalities not present in controls or subjects who experience remission. This new knowledge of acute stress disorder and PTSD is highly significant because it is expected to improve our ability to: predict who is at nsk; illuminate possible ways to prevent the advance from early symptoms to chronic illness; and aid in the design of therapeutic interventions that will be more effective at each stage of the illness. This will help reduce the incidence of acute stress disorder and PTSD in the population and prevent the emotional, economic and other human costs associated with these disorders.